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Image Search Results
Journal: Cell death & disease
Article Title: TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.
doi: 10.1038/s41419-024-07305-1
Figure Lengend Snippet: Fig. 2 Apoptosis is the mode of cell death induced by concomitant TGFβ1 and MEKi treatment in melanoma cells. A–C Representative FACS plots of the three melanoma cell lines M130830 (A), M170117 (B) and M010817 (C) treated with combinations of TGFβ1 (10 ng/mL), MEKi (10 nM) and ZVAD (40 µM) for 72 h as indicated and stained with Annexin V and Propidium Iodide (PI) solution. D–F Live cell quantification of the FACS staining from (A–C). Experiments were performed in 3 independent replicates. P-values were calculated by one-way ANOVA and multiple comparisons for selected pairs with *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001. G–I Western blots for PARP, cCASP3, and β-ACTIN (ACTB) from whole cell lysates of one sensitive, M130830 (G) and two resistant melanoma cell lines, M170117 (H) and M010817 (I), treated with combinations of TGFβ1 and MEKi for 48 h as indicated. cCASP3 and cPARP levels were quantified relative to the loading control with the MEKi only condition set to 1 and shown below the blots.
Article Snippet: Stimulations were performed with
Techniques: Staining, Western Blot, Control
Journal: Cell death & disease
Article Title: TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.
doi: 10.1038/s41419-024-07305-1
Figure Lengend Snippet: Fig. 3 Double treatment induces a distinctive gene expression signature as compared to the individual treatments. A, B Heatmaps of bulk RNAseq data of a “sensitive” (A) and a “resistant” (B) human melanoma cell line, representing differentially expressed genes (p adjusted < 0.05) that are part of previously defined [36, 39] melanoma programs: AXL, MITF and the resistance program. The expression values are z-score normalized per row and genes are clustered using hierarchical clustering with euclidean distance. C, D Gene set enrichment analyses (GSEAs) of each program (p adjusted value < 0.05) under each condition compared to the vehicle control (DMSO) in a sensitive (C) and a resistant cell line (D). Running Enrichment Score is shown on the Y-axis, gene number on the x-axis. E, F Scores of TGFβ1, MEKi or TGFβ1 + MEKi treatment signatures represented in cell subpopulations previously identified by single cell RNAseq analysis in a xenograft melanoma model during BRAFi/MEKi treatment [37]. Violin plots show cell score distribution within each cell population in a sensitive (E) and a resistant (F) cell line. “SMC” = starved-like melanoma cell state. “NCSC” = neural crest stem cell state.
Article Snippet: Stimulations were performed with
Techniques: Gene Expression, Expressing, Control
Journal: Cell death & disease
Article Title: TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.
doi: 10.1038/s41419-024-07305-1
Figure Lengend Snippet: Fig. 6 Apoptosis signature genes cannot be used as predictive markers for favorable treatment with targeted therapy. A Schematic setup of patient-derived melanoma cell line processing. Melanoma cell biopsies were cultured in vitro before bulk RNAseq and the half maximal inhibitory concentration (IC50) for MEKi was determined by MTT assays. B Representation of MEKi IC50 values for the top 20 and bottom 20 patient-derived melanoma cell lines, grouped accordingly. P-values were calculated by Mann-Whitney test with *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001. C Bar plots showing correlation of MEKi sensitive and MEKi resistant cell lines with average gene expression of all genes of the TGFβ1 + MEKi-associated apoptosis signature. P-values were calculated by unpaired t-test with *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001.
Article Snippet: Stimulations were performed with
Techniques: Biomarker Discovery, Derivative Assay, Cell Culture, In Vitro, Concentration Assay, MANN-WHITNEY, Gene Expression
Journal: eLife
Article Title: Conservation of peripheral nervous system formation mechanisms in divergent ascidian embryos
doi: 10.7554/eLife.59157
Figure Lengend Snippet: ( A ) Schematic summary of caudal PNS specification and molecular regulators in Ciona intestinalis (adapted from ; ; ; ; , more details can be found in ). ( B–L ) Expression of the P. mammillata orthologs of the C. intestinalis caudal PNS genes. In situ hybridization of a late neurula for Msx ( B ), at early tailbud stages for Ascl.b ( C ), Klf1/2/4 (D), Nkxtun3 (E), Tox ( F ), Bhlhtun1 ( G ), Dlx.c ( H ) and Dlk ( I ); and at mid/late tailbud stages for Atonal ( J ), Pou4F ( K ), and Celf3.a ( L ). ( M–Q ) Expression of Phmamm-Klf1/2/4 at early tailbud stages in control embryos ( M ), following electroporation of pFog >Ciinte.Admp ( N ) or pFog >Ciinte.Noggin ( P ); or following treatment with Bmp4 protein ( O ) or Dorsomorphin ( Q ). ( R–U ) Expression of Phmamm.Pou4F at late mid/late tailbud stages in control embryos ( R ), following treatment with Bmp4 protein ( S ), DAPT ( T ) or a combination of Bmp4 and DAPT ( U ). Embryos are shown in lateral view with dorsal to the top and anterior to the left. Scale bars: 50 μm.
Article Snippet: P. mammillata embryos were treated with 150 ng/ml
Techniques: Expressing, In Situ Hybridization, Control, Electroporation
Journal: BMC Developmental Biology
Article Title: Interleukin-6 increases inner cell mass numbers in bovine embryos
doi: 10.1186/s12861-019-0182-z
Figure Lengend Snippet: Transcript abundances for IL6 , IL6R and IL6ST from zygotes, 2-cell embryos, 8-cell embryos, morulae and blastocysts. Total RNA was isolated from 3 to 5 pools of 10 embryos from each developmental stage before reverse transcription. The relative abundance of each target transcript is expressed as fold change from the embryo stage containing the lowest abundance for the specified transcript by using the 2 [-ddCt] approach. Corresponding means and SEMs are indicated by the bars. Different superscripts within each transcript indicates differences ( P < 0.05)
Article Snippet: For all studies, a
Techniques: Isolation, Reverse Transcription
Journal: BMC Developmental Biology
Article Title: Interleukin-6 increases inner cell mass numbers in bovine embryos
doi: 10.1186/s12861-019-0182-z
Figure Lengend Snippet: Cleavage and blastocyst formation across each study
Article Snippet: For all studies, a
Techniques:
Journal: BMC Developmental Biology
Article Title: Interleukin-6 increases inner cell mass numbers in bovine embryos
doi: 10.1186/s12861-019-0182-z
Figure Lengend Snippet: Embryonic ICM and TE cell counts in Day 8 blastocysts
Article Snippet: For all studies, a
Techniques:
Journal: BMC Developmental Biology
Article Title: Interleukin-6 increases inner cell mass numbers in bovine embryos
doi: 10.1186/s12861-019-0182-z
Figure Lengend Snippet: Representative images of differential cell staining in blastocysts collected at day 8 post-fertilization. Embryos either received 0 or 100 ng/ml IL6 beginning at day 5 post-fertilization. Panel A: Blastocysts were harvested at day 8, fixed, immunostained, and physically flattened between a slide and coverslip. Photographs represent a single plane of focus. Nuclei representing TE are indicated by CDX2 + /DAPI + staining (green) and the ICM nuclei are CDX2 − /DAPI + (blue). Control embryo number 1 had 42 ICM cells and 94 TE cells, while control embryo number 2 had 53 ICM cells and 120 TE cells. IL6-treated embryo number 1 had 86 ICM cells and 99 TE cells, while IL6-treated embryo number 2 had 76 ICM cells and 143 TE cells
Article Snippet: For all studies, a
Techniques: Staining, Control
Journal: BMC Developmental Biology
Article Title: Interleukin-6 increases inner cell mass numbers in bovine embryos
doi: 10.1186/s12861-019-0182-z
Figure Lengend Snippet: Pooled ICM cell counts and ICM to TE ratios from all studies. All 100 ng/ml treatments of IL6 and associated controls were utilized, regardless of time point of treatment. No other doses of IL6 (1, 10 or 200 ng/ml) are included in this figure. Data from different studies are indicated by different symbols. Panel A : Individual ICM counts for embryos receiving either no treatment or 100 ng/ml IL6. Panel B : Individual ICM:TE ratios for embryos receiving either no treatment or 100 ng/ml IL6. Corresponding means and SEMs are indicated by the bars. Different superscripts within each panel indicates differences ( P < 0.05)
Article Snippet: For all studies, a
Techniques:
Journal: BMC Developmental Biology
Article Title: Interleukin-6 increases inner cell mass numbers in bovine embryos
doi: 10.1186/s12861-019-0182-z
Figure Lengend Snippet: Primers used for quantitative RT-PCR
Article Snippet: For all studies, a
Techniques: Sequencing
Journal: Nature Neuroscience
Article Title: Aging and injury drive neuronal senescence in the dorsal root ganglia
doi: 10.1038/s41593-025-01954-x
Figure Lengend Snippet: a , Representative images of SA-β-gal activity staining (blue) in the lumbar DRG of young (11–16 weeks) and aged (20–24 months) mice. Percent SA-β-gal-positive pixels per DRG area (right) ( n = 6 young, 5 aged mice; two-tailed unpaired t -test, P = 0.0153). Scale bar, 100 µm. b , Representative RNAscope images for senescence markers p21 and p16 with SASP factor IL6 in whole DRG section. Scale bar, 100 µm. c , d , Quantification of neuronal expression of each marker ( c ) or in combination ( d ) expressed as a percent of total DRG neurons ( n = 5 young, 4 aged mice, two-tailed unpaired t -test, p21 + , P = 0.0014; p16 + , P = 0.006; IL6 + , P = 0.0031; p21 + IL6 + , P = 0.0005; p16 + IL6 + , P = 0.3076; p21 + p16 + IL6 + , P = 0.1560). e , Analysis of IL6 -expressing DRG neuron population to show co-expression with senescence markers p21 and/or p16 in young and aged mice ( n = 5 young, 4 aged mice). f , Quantification of IL6 protein levels by ELISA assay in young or aged plasma ( n = 6 young, 5 aged mice, two-tailed unpaired t -test, P = 0.0474). All data are expressed as the mean ± s.e.m. NS, not significant.
Article Snippet: For in vitro (culture) preparations, coverslips were pre-incubated with either
Techniques: Activity Assay, Staining, Two Tailed Test, RNAscope, Expressing, Marker, Enzyme-linked Immunosorbent Assay, Clinical Proteomics
Journal: Nature Neuroscience
Article Title: Aging and injury drive neuronal senescence in the dorsal root ganglia
doi: 10.1038/s41593-025-01954-x
Figure Lengend Snippet: a , Schematic of SNI and DRG tissue analysis timepoints (BioRender). b , qPCR from lumbar DRG in young (11–16 weeks) mice ( n = 4 control; n = 4 SNI young mice; two-tailed unpaired t -test; Supplementary Table ). c , Left, RNAscope image of DRG slice in young mice. Scale bar, 100 µm. Right, number of DRG neurons expressing p21 (upper) or p16 (lower) in young mice ( n = 5 uninjured mice, n = 4, 7-day and 3-week post-SNI mice, n = 3, 7-week post-SNI mice; one-way ANOVA, p21 : uninj versus 7 days or 3 weeks, P < 0.0001; uninj versus 7 weeks, P = 0.0002. p16 : uninj versus 3 weeks, P = 0.0117; uninj versus 7 weeks, P = 0.0002; 7 days versus 7 weeks, P = 0.0085). d , e , Re-analysis of Renthal et al. . RNA-seq dataset using young adult mouse DRG. d , Percentage of p16 ( Cdkn2a + )-expressing senescent cells relative to all DRG cells after ScNT. Cells are negative for Lmnb1 and Top2a to filter out any nonsenescent cells. Glia, satellite glia and Schwann cells; Immune & other cells, neutrophils, macrophages, B cells, fibroblasts, endothelial cells and pericytes; Neuron, all DRG neurons. Dot plot ( e ) of senescence marker gene expression by DRG neurons after ScNT. SenMayo genes are significant, at least one timepoint (Supplementary Table ). f , RNAscope image of DRG slice in aged (20–24 months) mice. Scale bar, 100 µm. Number of DRG neurons expressing either p21 (right) or p16 (right) in aged mice ( n = 4 uninjured mice, n = 3 post-SNI mice/timepoint; one-way ANOVA, p21 : uninj versus 7 days, P = 0.0335; uninj versus 3 weeks, P = 0.0298. p16 : uninj versus 7 days, P = 0.0182; uninj versus 3 weeks, P = 0.0009; uninj versus 7 weeks, P = 0.0008). g , p21 + p16 + co-expressing DRG neurons ( n = 5 young uninjured mice, n = 4 young 3-week post-SNI mice; n = 4 aged uninjured mice, n = 3 aged 3-week post-SNI mice; one-way ANOVA, young uninj versus SNI, P = 0.0002; aged uninj versus SNI, P < 0.0001; young SNI versus aged SNI, P = 0.0003). h , p21 + p16 + IL6 + (asterisk) neuron by RNAscope. Scale bar, 10 µm. i , IL6 + DRG neurons co-expressing p21 and/or p16 ( n = 5 young uninjured mice, n = 4 aged uninjured mice, n = 4 young 3-week post-SNI mice, n = 3 aged 3-week post-SNI mice; one-way ANOVA; Supplementary Table ). j , IL6 + DRG neurons co-express p21 and/or p16 at 3 weeks after SNI ( n = 3 mice per group). All data are mean values ± s.e.m. Ag, aged; d, days; h, hours; NS, not significant; wk, weeks; Yg, young.
Article Snippet: For in vitro (culture) preparations, coverslips were pre-incubated with either
Techniques: Control, Two Tailed Test, RNAscope, Expressing, RNA Sequencing, Marker, Gene Expression
Journal: Nature Neuroscience
Article Title: Aging and injury drive neuronal senescence in the dorsal root ganglia
doi: 10.1038/s41593-025-01954-x
Figure Lengend Snippet: a , Analysis of cell diameter (µm) of p21 + IL6 + , p16 + IL6 + or p21 + p16 + IL6 + co-positive neurons in the DRG at 3 weeks after nerve injury in young (11–16 weeks) and aged (20–24 months) mice (young: n = 215 p21 + IL6 + neurons; n = 51 p16 + IL6 + neurons; n = 102 p21 + p16 + IL6 + neurons; aged: n = 155 p21 + IL6 + neurons; n = 21 p16 + IL6 + neurons; n = 46 p21 + p16 + IL6 + neurons). b , Representative RNAscope images of young or aged DRG co-labeled for the ion channel Trpv1, senescence marker p21 and SASP factor/cytokine IL6. Merged images also have DAPI overlay (gray). For IL6 signal, intense puncta signal with white center are positive neurons, and fainter/dull blue is background. Arrows: Trpv1 + senescent neurons; asterisks: Trpv1 − senescent neurons. Scale bars, 100 µm and 20 µm (insets). c , d , Quantification of Trpv1 neuron population and its co-expression with p21 and/or IL6 in young ( c ) and aged ( d ) L3/4 DRG of uninjured (controls) and 3 weeks after SNI ( n = 3 uninjured young mice, n = 972 Trpv1 + neurons; n = 3 SNI young mice, n = 1,548 Trpv1 + neurons; n = 4 uninjured aged mice, n = 1,056 Trpv1 + neurons; n = 3 SNI aged mice, n = 1,292 Trpv1 + neurons). wk, weeks.
Article Snippet: For in vitro (culture) preparations, coverslips were pre-incubated with either
Techniques: RNAscope, Labeling, Marker, Expressing
Journal: Nature Neuroscience
Article Title: Aging and injury drive neuronal senescence in the dorsal root ganglia
doi: 10.1038/s41593-025-01954-x
Figure Lengend Snippet: a , Representative traces from p16 -expressing neurons demonstrating repetitive firing (left), hyperpolarization-activated current (Ih) presence (middle) and the firing parameters rheobase and AP latency (right). b , Clusters identified with the hierarchical density-based algorithm HDBSCAN after UMAP alignment of individual neurons constructed with diameter (range, 14–41 µm), firing properties and intrinsic currents. Discrete clusters – are identified by color ( n = 82 recorded DRG neurons from young (11–16 weeks) and aged (20–24 months) mice). UMAP highlighting senescence marker p16 (orange) ( c ), p21 (pink) ( d ) and the SASP factor IL6 (blue) ( e ). f , Heatmap depicting parameters from left to right as follows: clusters (cool gradient), gene expression (black, no expression; light teal, expression), diameter and physiology parameters (warm gradient; higher normalized values are lighter and lower values are darker). Senescence marker p16 and SASP factor IL6 groups contain neurons with high-firing phenotypes (>100 total APs fired during current steps), which is outlined over increasing depolarizing current steps (lower left panel). Ih current amplitude was also measured at decreasing hyperpolarizing steps (lower right panel). g , Senescent neurons (p21 in magenta, p16 in orange and IL6 in blue) display the DRG nociceptor-associated property of wide APs (half-width above 0.5 ms, gray dotted line). h , IL6 application increases evoked firing in senescence marker-expressing neurons in monolayer culture (155.5 ± 18 APs, n = 26 cells from 11 mice for control; 209.7 ± 19.06 APs , n = 27 cells from 13 mice for IL6 application; U = 234.5, P = 0.038, two-sided, Mann–Whitney test; neuronal expression of p21 in magenta, p16 in orange, p21 and p16 in green and p21 and IL6 in blue). All data are mean values ± s.e.m.
Article Snippet: For in vitro (culture) preparations, coverslips were pre-incubated with either
Techniques: Expressing, Construct, Marker, Gene Expression, Control, MANN-WHITNEY
Journal: Nature Neuroscience
Article Title: Aging and injury drive neuronal senescence in the dorsal root ganglia
doi: 10.1038/s41593-025-01954-x
Figure Lengend Snippet: a , b , Representative RNAscope images from young or aged human L4 DRG showing expression of p21 and p16 senescence markers (enlarged left images with DAPI; scale bar, 100 µm). The large globular signal present in both channels is autofluorescent lipofuscin and not RNAscope signal (small puncta). c , Quantification of p21 + and p16 + neurons in the young and aged human DRG as a percent of total DRG neurons ( n = 2 young female (32-year-old and 33-year-old); n = 2 aged male/female (65-year-old) DRG). d , Quantification of IL6 -expressing neurons as a percent of total DRG neurons ( n = 2 young female (32-year-old and 33-year-old); n = 2 aged male/female (65-year-old) DRG). e , Analysis of IL6 + neuron population and quantification of the co-expression of senescence markers p21 and/or p16 . f , Quantification of neurons co-expressing senescence markers p21 and/or p16 with IL6 as a percent of total DRG neurons ( n = 2 young female (32-year-old and 33-year-old); n = 2 aged male/female (65-year-old) DRG). g , Percent of DRG neurons that are ATF3 + in young and aged human DRG ( n = 2 young female (32-year-old and 33-year-old); n = 2 aged male/female (65-year-old) DRG). h , Example image depicting a single human neuron positive for ATF3 (nuclear-localized, immunohistochemistry) and p21 (RNAscope, puncta). Scale bars, 20 µm. Analysis of ATF3 + neuron population and quantification of the co-expression with p21 in young and aged human DRG (right, donuts) ( n = 64 young ATF3 + DRG neurons, n = 54 aged ATF3 + DRG neurons). i , Total percentage of TRPV1 + neurons as a percent of total DRG neurons in young and aged human DRG. Quantification of the subsets of TRPV1 + neurons that co-express either p21 or p16 by RNAscope (boxed right) ( n = 2 young female (32-year-old and 33-year-old); n = 2 aged male/female (65-year-old) DRG). j , Single representative human neurons (quantified in k ) showing co-expression of TRPV1 with p21 and/or p16 . DAPI in gray. Scale bars, 20 µm. k , Venn diagram of human DRG neurons that express TRPV1 , p16 and p21 . Aged DRG display a greater overlapping fraction of TRPV1 + neurons expressing either or both senescence markers p21 and p16 compared to young neurons. n = 2 young female (32-year-old and 33-year-old); n = 2 aged male/female (65-year-old) DRG. All data are mean values ± s.e.m.
Article Snippet: For in vitro (culture) preparations, coverslips were pre-incubated with either
Techniques: RNAscope, Expressing, Immunohistochemistry
Journal: Nature Neuroscience
Article Title: Aging and injury drive neuronal senescence in the dorsal root ganglia
doi: 10.1038/s41593-025-01954-x
Figure Lengend Snippet: Cell diameters (µm) of human DRG neurons co-expressing either p21 + IL6 + , p16 + IL6 + , or p21 + p16 + IL6 + , as a percent of total neurons counted in each population in young ( a ) and aged ( b ) DRG (n = 2 young female (33yo and 32yo) DRG: n = 19 p21 + IL6 + DRG neurons, n = 96 p16 + IL6 + DRG neurons, n = 71 p16 + p21 + IL6 + DRG neurons; n = 2 aged male and female (65yo) DRG: n = 126 p21 + IL6 + DRG neurons, n = 84 p16 + IL6 + DRG neurons, n = 271 p16 + p21 + IL6 + DRG neurons).
Article Snippet: For in vitro (culture) preparations, coverslips were pre-incubated with either
Techniques: Expressing